Fragile X Syndrome – causes, symptoms, diagnosis, treatment, pathology


With Fragile X syndrome, sometimes just called
Fragile X, the “X” refers to the X chromosome, where the disease gene is located. The “fragile” refers to the fact that
under a microscope, the X chromosome looks fragile or broken at the site of the mutation. That’s because the chromatin which makes
up the chromosome gets really condensed at that point. Fragile X is a genetic disease that affects
various organ systems. Now, the gene for Fragile X is called FMR1,
which stands for Fragile X mental retardation 1. Mental retardation is the old term for intellectual
disability, which is one of the key features of Fragile X syndrome. The FMR1 gene has a triplet repeat, or trinucleotide
repeat, which means that a group of three DNA nucleotides is repeated multiple times
in a row. In FMR1, it’s the nucleotides cytosine,
guanine, and guanine, or CGG. These CGGs are found in the 5’ untranslated
region of FMR1. A 5’ untranslated region is the part of
DNA at the beginning of the gene that’s made into mRNA but not protein, and helps
modulate gene expression. Just upstream from the 5’ untranslated region
is FMR1‘s promoter, the region that causes the gene to be transcribed to mRNA, which
is usually turned on. Expressed FMR1 mRNA gets translated into Fragile
X mental retardation protein, or FMRP, and it helps in development of the brain and other
tissues. In Fragile X syndrome, there is a repeat expansion,
meaning there’s an increased number of CGG repeats in the gene. This repeat expansion is caused by slipped
mispairing, which is where the enzyme DNA polymerase gets confused when copying a repetitive
sequence. DNA polymerase loses its place among the FMR1
triplet repeats and goes back to recopy what it already just copied. This is like getting lost in a video and watch
the same part over and over. But since DNA polymerase is making copies,
the effect is an increase, or expansion, of the number of repeats. The normal number of CGG triplets is 5-44. Alleles with 45 to 54 CGG repeats are called
intermediate expansion alleles and they don’t cause any symptoms. Alleles with 55 to 200 CGGs are called premutation
alleles, and they can cause some mild symptoms. Finally if an allele has over 200 CGGs, then
it’s considered a full fragile X syndrome mutation and can make the chromosome take
on its distinctive look. Alleles can tend to get longer and longer
as DNA polymerase becomes more and more unstable copying the longer stretches of repeats, so
an intermediate expansion allele can become a premutation allele, and a premutation allele
can expand to become a full fragile X syndrome mutation. The repeat expansion attracts a DNA methylase
enzyme to the site and causes the cytosines in the CGG repeats to become methylated. These bulky methyl groups cause the chromatin
– which is DNA wrapped around histones – to condense. When it’s in a condensed form, regions of
the FMR1 gene can’t be bound by transcription factors. As a result, the promoter of the FMR1 gene
is locked in the “off” state, so its product FMRP can’t be made in adequate amounts,
and that leads to Fragile X syndrome. Fragile X can cause intellectual disability,
delayed speech, and delayed motor development, for example learning to walk at eighteen months
instead of twelve. Many children with Fragile X also develop
autism, ADHD, and seizure disorders. Individuals with Fragile X syndrome can have
develop classic physical features as well – like a long and narrow face, a prominent
jaw and forehead, and large ears that stick out. These facial features might not be seen in
an infant, but become obvious as the child becomes older. Males can also have larger than normal testes
after puberty. Fragile X is typically milder in females than
males, and many females with the Fragile X mutation have no symptoms due to reduced penetrance. This is because females have a normal backup
copy of FMR1 on their other X chromosome. Skewing of X-chromosome inactivation which
the process in development where each cell picks one X-chromosome to rely on – can
make a female more or less likely to show symptoms. Interestingly, FMR1 expansions are almost
always inherited from the mother. Premutation carriers have too few repeats
to get Fragile X, but they can have other symptoms, for example Fragile X-associated
tremor ataxia syndrome, or FXTAS. FXTAS is an adult-onset, progressive neurological
disease that includes: intention tremor, which shaking when movement is initiated; ataxia,
which can make walking difficult; memory and cognitive problems, and white matter changes
detected by brain MRI. Female premutation carriers can also get FMR1-related
primary ovarian insufficiency, where the ovaries shut down early and menopause starts before
age 40. Fragile X, FXTAS, and FMR1-related primary
ovarian insufficiency are diagnosed by a DNA test that counts the number of CGG repeats. It’s important to make the diagnosis in
order to counsel the individual about the risk of these diseases in current and future
family members. FMR1 testing is often done for individuals
with intellectual disability, developmental delay, or autism, and carrier testing can
be done for pregnant women. Treatment of Fragile X is directed at individual
symptoms, for example special education for intellectual disability, stimulants for ADHD,
and evaluation by a reproductive endocrinologist for premature ovarian insufficiency. Alright, as a quick recap, Fragile X syndrome
is a genetic disorder caused by expansion of over 200 CGG triplet repeat in the FMR1
gene on the X chromosome. It’s more likely to cause symptoms in males
than females, and these symptoms include intellectual disability and autism, a long, narrow face,
a prominent jaw and forehead, large ears, and large testes in adolescent males. Premutation carriers, who have an intermediate
number of repeats, can have Fragile X tremor ataxia syndrome and premature ovarian failure.

Rhode Island Hospital’s Outpatient Dialysis Program

Rhode Island Hospital’s Outpatient Dialysis Program


The essence of dialysis really is filtering
the blood, getting waste products that the kidneys are not normally able to get rid out
of the blood because those waste products build up and make people very ill. People
with kidney failure have, as a big problem, a lack of ability to get rid of the waste
products that we all generate, everyday in the course of normal living. When those waste
products build up, people can get ill and we need to get rid of them in some way. So,
dialysis involves a system where fluid runs through a filter, runs past patients’ blood,
and substances in the blood, that are dangerous or hazardous, got transferred from the blood
into this fluid, which is flowing past the blood and then get excreted. Dialysis in the
state continues to make a tremendous difference for the lives of about a thousand people in
our state who have chronic kidney disease. We started our program in 2009, October 2009,
and we currently have about 85 patients in both centers, with the center on Chapman Street
and our center right her in East Providence. It’s our presence on the East Bay, so we hope
to make that easy for our patients who live in the East Bay and in southeastern Massachusetts,
as well to use this facility. People shouldn’t have difficulty getting here or parking here.
It’s a beautiful, beautiful facility, as you can see here. It’s nice and airy and light.
Gets lots of natural light in, which I think makes people, uh, makes people feel better.
And again, here, we offer in center dialysis and offer the opportunity for patients to
choose the other types if dialysis, as well, home hemodialysis and peritoneal dialysis
by using our facility at Chapman Street at the same time. We have 12 bays here in East
Providence and in Chapman Street, we have 18 bays. At Chapman Street, we offer dialysis
till about 10 o’clock at night for people who will go to school, people who work during
the day. So about one third of the patients get dial is starting at about 5 o’clock at
night and go to about 10:00 at night, as well. We have televisions available. Patients have
cable. They can look at television during the treatment. This is Wi-Fi accessible, so
that people can bring their laptops in, surf the internet, do email through their work,
etc. when they’re here. The cartridges that we use, which are right here, are made of
material that actually is much more compatible with patient’s blood so people don’t get reactions
to it. The machines allow a very rapid blood flow, so that makes the treatment very efficient
and can sometimes shorten the treatment. The dialysate, which is specially processed water
that we use that the patient’s waste products go into and the patient’s are exposed to,
is now very very closely monitored, kept bacteria free. The machines, themselves, are automated
and can pick up any problems that may occur during the dialysis treatment. The machines
don’t let us take too much fluid off, for example. They closely monitor that and the
machines kind of serve as a medical record to also tell us about how the treatment’s
been going. We have a multidisciplinary approach her and many people are involved in a patient’s
care. The most important, by far and away, is the patient, him or herself, who sits absolutely
at the center of our care plans and of our care, surrounding the patient, our physicians,
and nephrologists, interventional radiologists, transplant surgeons, general surgeons, trained
specialized nephrology nurses, dialysis technicians, social workers, and dieticians, who have a
special training and expertise and the care of people with kidney disease. But again,
the most important member of that team, by far, is the patient.

How To Build A Hospital

How To Build A Hospital


In Western Sydney, healthcare needs are evolving as our population grows and ages and people live longer. We’re transforming the way we deliver healthcare, and the role that hospitals play in our community to embrace emerging technologies and changing community expectations. Here at Westmead, we are part of the most exciting redevelopment of a health precinct in Australia. There’s a lot happening and we want to share with you all the work that goes into building the first part of our Redevelopment – a new hospital building. How do you build a hospital? First comes the planning. Then comes the building. The planning can take several years, as there’s a lot to consider. We care about our patients and the community and we have to ask ourselves some big questions. How can we help people to be healthy over the next 50 years? How can we better integrate our world-class research and education? How can we design and building infrastructure for the future? What does world-class clinical care look like for the next generation? To answer these questions we have to know what our health needs are now and how they will change in the future. We have to look at new ways of working. We have to develop the right models of care for our
patients. To do all of this we speak to our staff, patients, carers and our community. This is all done through project user groups called PUGs. PUGs work closely with patients, carers and architects. They take all the questions that we asked ourselves and the answers to design the new hospital building. PUGs are used at every stage of the hospital development. Find out who your PUG representative is and how to get involved. We really want to hear from you. So what does a PUG work on first? They develop a Functional Brief. The Functional Brief tells the planners how you work, how you deliver healthcare and how your department works with other areas of the hospital. This phase also sees us work out how other important services interact with clinical service delivery, like education and
research. A big focus is on innovation and finding a better way to do things. The next phase is Concept Design and this is where it gets really exciting. We get to start looking at drawings and pictures of the building, its size and location. From there we look at flow – how the patients and services, as well as staff, will move throughout the building and even how information travels between departments and across the precinct as a whole. But we go even further and look at how the precinct is going to interact with the transportation networks of the city and the surrounding areas. We have to test this again and again to get it right, even going back to the Functional Briefs and the Concept Design to make sure we’re holding true. That’s when we move to Schematic Design. It includes detailed architectural plans and layout for each floor, and it is at that time we have to do the budget planning to make sure that we stay on budget and meet our priorities. Then are ready for Detailed Design. This literally gives us the nuts and bolts of the new building – right down to the power points and the furniture. This is the plan the builder uses to create our new building. While the design is finalised by the Local Health District and the project team, through the tender and construction process, we must focus on transitioning into the new building. . You will often hear this referred to as Commissioning. There is Building Commissioning, where the project team ensure things like electricity, IT and air-conditioning are working. We must focus on Operational Commissioning. Our tools of the trade may have moved, departments that we may connect with may be further away or closer, and new technologies may be in our workplace. We must adapt to new ways of working and we must do that now. And that’s how you building a hospital. The planning alone can take over a year. We use the time between now and the opening of the new to introduce new models of care, to test new processes and procedures, to get used to doing things differently before we make the move, and to work out how we stay connected with with teams and services in the existing buildings. You’ll be hearing plenty from the project team because it’s a long and important journey that we are on. You see we’re not just building a hospital, we’re building new services, new networks of care and better ways of doing things. We’re building health and we’re transforming lives.

AMBULANCE – Court métrage (Horreur Fantastique) Céleste Grant 2020


This video is not recommended for children under 10 years old. Well, all the papers for the vehicle are in order. Insurance, registration card, certificate of non-pledge, All you have to do is sign the vehicle transfer declaration. Right… So now we’re going to see the vehicle. CÉLESTE GRANT
Presents Here’s the thing. Ah yeah ok, you left everything from the ambulance. Yes, absolutely, we didn’t change anything, we left everything, the equipment, the cupboards, The drawers, everything is as before. – It’s original!
– But go ahead, go up, we’ll visit. And there you even have lights on the side up there. Ah! – It’s great, it’s really cool!
– And there, at the very bottom on the left, you have a switch. If you press it, it makes speaker with the front cabin. “Right here, you can communicate with the driver. ” There you go … The keys are yours! Thank you. Uh … Since it’s an old ambulance, Does that mean there were deaths in it? AMBULANCE “Hello?” ” Yes, I call you back. You didn’t tell me that there was a noise at the back when you are driving. ” A noise ? Ah no, I assure you, there is no noise. ” I seemed to have heard something … “No, logically there is nothing, but call me if there is a problem. ” Well, listen, I’ll be careful, then I’ll see. – “All right. ”
– Thank you. Shit! AMBULANCE A Celeste Grant movie With
Maximilien Dulac With
Alice Aglaghanian / Allan Christopher Music
CO.AG – Music Produced by
CELESTIAL GRANT Thanks to
TIPEURS © 2018 – All Rights Reserved Thank you for watching my short AMBULANCE I hope you liked it. I really invite you to give me your opinion and to react in the comment space of this video. Also, don’t hesitate to put a thumbs up if you liked this little film. For the record, AMBULANCE was completed in just a few hours. We filmed the daytime scenes in just 1.5 hours, And the night scenes in 2 hours max. It was like a challenge we gave ourselves. Me, behind the camera, the main actor and, let’s say, “the ghost”. Of course, the vehicle occupies an important place in the scenario. But I’m not going to detail now, Because a Making of is now available on this Youtube channel. Or at least it will be soon. Find the link of it into the video description. Don’t hesitate to go see the Making of to get more details on this film, The special effects, and filming anecdotes that we encountered. Admittedly, it is a film with certain small defects. We could criticize, for example, the acting not always correct. But I remind you that they are not precisely actors, But just my friends who agreed to play in my movie. But what I really like about this movie : AMBULANCE, is that it proves that with very little budget and a lot of energy and passion, We can still tell a story, Which, casually, transmits an atmosphere, and, I like to think so: A certain little thrill of horror, anguish, fantastic type. AMBULANCE is one of those kind of achievements that raise awareness, That we can really achieve beautiful things without budget, when we’re motivated. right, I stop here. If you like fiction, short films, web series, Don’t hesitate to subscribe to this channel by activating the bell. I remind in passing that I have other YouTube channels, on which I experiment with other forms of creations. Like music, Urbex or Gaming. All information is in description. I’m Céleste Grant, see you soon, For new videos.

Malleolar Zone Algorithm | Ankle Fracture


In this video we are going to present
the Malleolar Zone Algorithm used to exclude fractures of the malleolar zone in children with acute ankle injuries Get our very own assessment E-book and mobile app, links are in the video description! Hi welcome back to Physiotutors! The Malleolar Zone Algorithm was developed by Dayan et al. (2004) Their goal was todevelop a maximally sensitive clinical prediction rule to identify fractures after ankle injuries in children younger
than 18 years of age This includes fractures of the tibia, fibula or talus. They argued the importance of such a new CPR as validation studies of the Ottawa
ankle rules in a population of children resulted in conflicting results. A recent
systematic review by Bareldts et al. (2017) pooled the results of three studies
investigating the Malleolar Zone Algorithm and reports a positive
likelihood ratio of 1.24 and negative likelihood ratio of 0.23 and in
our opinion it has a moderate clinical value ((to exclude fractures in children) The Malleolar Zone Algorithm goes
as follows and aims to identify significant or high-risk fractures in
children younger than 18 years of age after acute twisting ankle injury:
1. you will check for tenderness at any area of the lateral or medial malleolus.
In case the first step is negative assess whether the fibula is tender just
proximal to the malleolus. If that is the case there’s a high risk for fracture. If
you found tenderness of the malleolus during the first step, check if the child
is able to walk four steps. If the child is unable to do so, there’s a higher risk
for fracture. Is the child able to walk four steps, but there’s swelling over the
lateral or medial malleolus, then there’s – again – a high risk for fracture, which
would warrant radiographic investigation. Alright, thanks for watching! The authors
have also developed a CPR for the mid-foot so go check out this video next
by clicking or tapping on the left! Make sure to hit the “like” button before you leave and check the links in the video description for info on our ebook as
well as our app and links to our other social media accounts where we post on a daily basis! As always this was Andreas for Physiotutors, I’ll see you next time –
bye!

How a Helijet Air Ambulance Pilot Finds Peace In The Chaos

How a Helijet Air Ambulance Pilot Finds Peace In The Chaos


(radio chatter) Helijet, Bree speaking. Sure, I can check the weather.
I’ll give you a call right back. Hi Jordan, it’s Bree at Helijet. Cooper just called me about
Campbell River to Victoria. Go ahead with the details.
Ok, sounds good. We’ll just give the crew a
brief, get some fuel, and then we’ll give you a
call in the air on our way to the airport in
Campbell River. We fly patients for the BC
Air Ambulance Service where ever they
dispatch us to. We’re on call here at
Vancouver International. 24 hours a day.
Seven days a week. Generally, we’re bringing
the crew to them to stabilize the patient, get
them to a hospital to an emergency room. We either get a phone call
or a text messege. When it’s a text it’s
an auto launch which I think for all of us,
it elicits a very strong (quick breath) “Ok, let’s go!” And, “Where are we going?”
“How’s the weather?” And all the other stuff that
starts to come into play. (radio chatter) It’s very fulfilling to move
people that need help. I mean, we are a really
small part of it. We’re just the bus drivers. We’re picking them up
and getting them where they need to be. Paramedics are really saving
lives in the back but it’s rewarding to be
a part of that team. And to be a little piece in the
puzzle that helps patient care. While the environment that
we work in can be really spontaneous and demanding, when we are working and
focusing, it’s very calm and methodical. (radio chatter) Flying is so peaceful to
me. There’s just sky, water, ground, and a little
bit of air sound going past the aircraft. the aircraft.
That on its own is
just beautiful That on its own is
just beautiful but then the bonus of being
able to help people is really rewarding. Seeing the fragility of life,
it just makes you so aware of how short your life can be and to make the most of
absolutely every day. I talk to my kids about
that a lot. It’s such a perfect
balance for me. To be able to be mom and pilot
in a really rewarding job. In a really rewarding role. Always listen to your heart
because your heart will know what you are meant to do. And then when you are doing
what you are meant to do there will be a sense of calm and all will be right.

North West Air Ambulance Patient Story – The Boy Of Steel

North West Air Ambulance Patient Story – The Boy Of Steel


(Music starts) (Corinne Mason) It was on a Sunday evening
that we joined the M6 and as we were on the M6 my husband and myself could see and smell
diesel. Just as we’d noticed it, the lady in front of us, hit the diesel in her car,
spun and crashed into the crash barrier. Because we could see diesel in front of
us, we decided to pull over to the hard shoulder and get the children
out to safety. (Richard Mason) Well I got out of the car,
to walk down the hard shoulder to make sure the other driver was okay and as my family
were getting out the car, another two cars skid on the diesel and smashed into the car. (Noise of car skidding, crashing and
smashing into the car) Unfortunately, my son was getting out of the
car at the time, so I saw the car hit ours and then our car get pushed into the verge.
And my son go flying into the air and landing on the hard shoulder. (Music fades out) (New music starts) When I first got to him, he was broken on
the floor. He was unconscious. I didn’t know his breathing so I essentially
thought he was dead. (Corinne Mason) There was hundreds, if not
thousands of cars stopped still and I was just screaming and shouting, just thinking
we’d lost him. He was dead. As far as we were concerned he was unconscious, his head was
caved from the very top and all within five seconds. That split decision to try and get
him to safety, all went wrong. The land ambulance were the first people to
arrive. They were great. They got Fred into the ambulance and made an assessment. Well
almost instantly they decided that they needed the Northwest Air Ambulance. When the Air
Ambulance arrived, it was like a lifeline. It was like somebody had come to help us.
They were like heroes arriving. (Richard Mason) When he got to taken to the
helicopter, I was very distressed because he was obviously seriously injured but when
we saw the helicopter, we knew that he was going to get to where he needs to be quickly. (Corinne Mason) By Air Ambulance, it took
them fifteen minutes to get him to Liverpool Alder Hay Children’s Hospital but by car,
by land ambulance that would have taken an hour and a half. You know he could have bled
out. Anything could have happened but they got him there quickly and safely. (Music fades out) (New music starts) Fred had a decompressed skull after the accident,
which meant that his skull was pushed in, at the top corner. Fred was in Alder Hay for
only a week but he got the nickname, the boy of steel because they couldn’t believe that
this little boy that had been brought in under these circumstances had made such a miraculous
recovery. There was no long-term damage and we managed to get him home a week later. After
the surgery it was just a case of looking after him and making sure that he was
okay – physically, mentally and emotionally. We’re extremely thankful to the Northwest
Air Ambulance and we’ll never stop saying thank you. The Northwest Air Ambulance changed
the outcome for us. We don’t know what would have happened but what I do know is that time, the quickness of the journey changed
Fred’s outcome. (Richard Mason) The Northwest Air Ambulance
– we didn’t think about it one bit until we really needed it and I suppose that’s the
point of it. You don’t know until you need it. So they need all the money they can get,
to make sure that they’re there when you need them. I think we’d do the same again. We’d pull
over, but it does make you aware of how dangerous the motorway can be and how quickly things
can change, because we went from (Richard starts to get upset) We went from just a normal Sunday afternoon
out, to what could be only described as the worst day of your life. So yeah, things can
change very quickly. Fred was a very lucky boy. On that day, The Northwest Air Ambulance
made a massive difference. He couldn’t have got to where he needed to be as quickly. He
couldn’t have got the care he needed that quickly. Even he realizes how lucky he is.
He is bouncy. He is bubbly. So thank you very much. (Corinne Mason) It’s really important that
people contribute to the Northwest Air Ambulance if they can. It’s a charity, so it needs people’s
support. (Richard Mason) We didn’t realise it until
after the accident that it was a charity. They need a lot of money, to help a lot of
people. There’s no other charity service that provides this type of quick response, high-value
care. Very well trained individuals. You know, at the flick of a switch they can be there. (Richard and Corinne’s children) Thank you
North West Air Ambulance because if it wasn’t you I wouldn’t be sat here with my brother
now. Thank you. (Music fades out)

Helping the Nation Save Lives Since 1877 – St John Ambulance

Helping the Nation Save Lives Since 1877 – St John Ambulance


[Song] Place your baby on a nice flat surface, and tilt
their head back – don’t be nervous! [Man’s voice] Wasn’t Steve supposed to be sorting out on Friday? [Football commentator] He’s milking the moment! Just goes to show – you don’t have to be a footballer… [Princess] Then, one gives up to five back blows [Trainer] … under one year old is choking, you’ll notice that they’ll be unable to cry, cough or breathe [Voiceover on historical clips]…the next part of the journey. There will be that
touch of a loving hand, the look that speaks more than a play full of words. When you’re fit enough to be flown back to a home hospital
you begin to… … the one-man ambulance which the St John’s man is
driving, but it’s so comfortable that I’ll be more than one man… [Child’s voice] My mummy, she fell off a chair and she’s moving, and she’s not even getting up… [Man] I just grabbed her and carried out five initial rescue breaths in the hallway. The paramedic popped his head round the back of the ambulance and shouted ‘Well done, she’s alive!’ I couldn’t believe it, I’d saved her. [Woman’s voice] I think it’s very important that
children learn first aid because if they didn’t people like Billy wouldn’t save
people’s lives. If Bill hadn’t been to St John Ambulance, I would be alive today.